title: Discovery and characterization of a unique mycobacterial heme acquisition system.
abstract: Mycobacterium tuberculosis must import iron from its host for survival, and its siderophore-dependent iron acquisition pathways are well established. Here we demonstrate a newly characterized pathway, whereby M. tuberculosis can use free heme and heme from hemoglobin as an iron source. Significantly, we identified the genomic region, Rv0202c-Rv0207c, responsible for the passage of heme iron across the mycobacterial membrane. Key players of this heme uptake system were characterized including a secreted protein and two transmembrane proteins, all three specific to mycobacteria. Furthermore, the crystal structure of the key heme carrier protein Rv0203 was found to have a unique fold. The discovery of a unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics.
authors.affiliation: Departments of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Tullius
authors.forename: Christine A
authors.initials: CA
authors.lastname: Harmston
authors.forename: Cedric P
authors.initials: CP
authors.lastname: Owens
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chim
authors.forename: Robert P
authors.initials: RP
authors.lastname: Morse
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McMath
authors.forename: Angelina
authors.initials: A
authors.lastname: Iniguez
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Kimmey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.forename: Julian P
authors.initials: JP
authors.lastname: Whitelegge
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Horwitz
authors.forename: Celia W
authors.initials: CW
authors.lastname: Goulding
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D006418:Heme / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D006418:Heme; D007501:Iron